Warwar Amir, Zargari Iren, Stein Nili, Zoubi Ibrahim, Muhammad Emad, Perek Shoshan, Naamneh Marwa, Preis Meir, Saliba Walid
Institute of Hematology, Lady Davis Carmel Medical Center, Haifa, Israel.
Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Int J Med Sci. 2025 Jun 23;22(13):3182-3190. doi: 10.7150/ijms.108258. eCollection 2025.
Inherited thrombophilia screening is widely performed in patients with venous thromboembolism (VTE). Although recent studies suggest that direct oral anticoagulants (DOACs) may provide comparable efficacy and safety to Vitamin K antagonists (VKAs) in this population, robust evidence to support their extensive use is still lacking. We aimed to evaluate the rates of VTE recurrence and overall bleeding in patients with inherited thrombophilia treated with DOACs versus VKAs, with particular interest in those with severe thrombophilia. Using the electronic database of the largest healthcare provider in Israel, we conducted a retrospective search for patients with a recorded VTE between 2012 and 2021 (the index event). Patients aged 18 or older at the time of diagnosis were included if they began treatment with either a DOAC or a VKA within 30 days of the index event, provided they had laboratory evidence of inherited thrombophilia. Patients were followed up for two independent outcomes (VTE recurrence and overall bleeding) until December 31, 2022 or until termination of follow-up due to death, switching from one oral anticoagulation class to another, or discontinuation of oral anticoagulation. Rates of VTE recurrence and overall bleeding were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). A total of 398 patients (median age 50.9±17.8, males 51.8%, severe thrombophilia 24.9%) were included. Among these, 230 patients (57.8%) were prescribed DOACs, while 168 patients (42.2%) received VKAs. The median follow-up for VTE recurrence and overall bleeding was 21.1 months and 20 months, respectively. Using the VKAs group as a reference, the hazard ratio for VTE recurrence on DOACs was 1.25 (95% CI, 0.23-6.7), and the hazard ratio for overall bleeding on DOACs was 0.33 (95% CI, 0.03-3.7). Restricting the analysis to 99 patients with severe thrombophilia (46 on DOACs, 53 on VKAs) showed no substantial differences in both efficacy and safety. Among patients with inherited thrombophilia treated with DOACs or VKAs, this study found no significant difference in the risk of recurrent VTE and observed a non-significant trend toward a lower risk of bleeding with DOACs.
遗传性易栓症筛查在静脉血栓栓塞症（VTE）患者中广泛开展。尽管近期研究表明，在这一人群中，直接口服抗凝剂（DOACs）与维生素K拮抗剂（VKAs）的疗效和安全性相当，但仍缺乏支持其广泛应用的确凿证据。我们旨在评估接受DOACs治疗与接受VKAs治疗的遗传性易栓症患者的VTE复发率和总体出血情况，尤其关注重度易栓症患者。利用以色列最大医疗服务提供商的电子数据库，我们对2012年至2021年期间有VTE记录（索引事件）的患者进行了回顾性检索。诊断时年龄在18岁及以上、在索引事件发生后30天内开始接受DOACs或VKAs治疗且有遗传性易栓症实验室证据的患者被纳入研究。对患者进行两项独立结局（VTE复发和总体出血）的随访，直至2022年12月31日，或因死亡、从一种口服抗凝剂类别转换为另一种、或停止口服抗凝治疗而终止随访。使用Cox回归比较VTE复发率和总体出血率，并报告为风险比（HRs）及95%置信区间（CIs）。共纳入398例患者（中位年龄50.9±17.8岁，男性占51.8%，重度易栓症占24.9%）。其中，230例患者（57.8%）被处方使用DOACs，168例患者（42.2%）接受VKAs治疗。VTE复发和总体出血的中位随访时间分别为21.1个月和20个月。以VKAs组为参照，DOACs治疗的VTE复发风险比为1.25（95%CI，0.23 - 6.7），DOACs治疗的总体出血风险比为0.33（95%CI，0.03 - 3.7）。将分析局限于99例重度易栓症患者（46例使用DOACs，53例使用VKAs），结果显示在疗效和安全性方面均无显著差异。在接受DOACs或VKAs治疗的遗传性易栓症患者中，本研究发现复发性VTE风险无显著差异，且观察到DOACs治疗的出血风险有降低趋势，但差异不显著。
